PB1722: EARLY T-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA: DIAGNOSIS AND TREATMENT CHALLENGES
Authors: Nour Siala, Fattouma Ben Sghaier, Yousra Fakhfakh Derbel, Imen Frikha, Mourad Chaari, Samia Menif, Halima Sennana, Moez Medhaffar, Jallel Gargouri, Taicir Rekik, Hela Menif, Ikram Ben Amor, Nour Louati
Journal: HemaSphere (2023)

Topic: 1. Acute lymphoblastic leukemia - Biology & Translational Research Background: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a distinct entity according to the updated (2016) WHO classification due to its particular immunophenotypic and genomic profile. The molecular genetic abnormalities and their prognostic impact in ETP-ALL patients are poorly understood. Moreover, the diagnosis and management of this entity is still challenging. Aims: We report a cohort of 10 cases of ETP-ALL and we compared their clinical characteristics, biological features, response to treatment and follow up data with other T-ALL immunophenotypic subtypes. Methods: We retrospectively reviewed data from patients newly diagnosed T-ALL in our laboratory and treated with the EORTC 58951 pediatric protocol or GRALL/GRAAPH adult protocol between 2013 and 2021. FC immunophenotyping (FCI) was performed in peripheral blood or bone marrow (BM) samples firstly on Epics XL® cytometer (BC) then on FACS Canto II ® (BD). Patients with ETP-ALL were identified on the basis of the following FCI (WHO 2016): CD1a and CD8-negative, CD5-negative or dim (<75% of blasts positive) with one or more stem cell/myeloid markers positive (≥25% of blasts positive). Patients demographics, ETP-ALL characteristics, response to treatment [response to prophase, complete remission (CR) and treatment related mortality (TRM)] and follow up data [relapse rate, overall survival (OS) and event free survival (EFS)] were collected. Results: Ten cases of ETP-ALL [5 children (median age= 8 years) and 5 adults (median age= 44 years)] were identified among 87 cases of T-ALL (11.5 %). Blood or BM smears concluded to ALL (8 cases) or undifferentiated AL (2 cases) with the presence of Auer-rod-like inclusions in the mature Neutrophils (2 cases). FCI categorized ETP-ALL (EGIL classification) as pro-T (2 cases) and pre-T (8 cases) subtypes. There were no significant differences in clinical and biological features between ETP-ALL and the others T-ALL. Moreover, both pediatric and adult ETP-ALL patients have an inferior good response to prophase (33% vs 55%; 33% vs 65%; respectively), a superior CR rate to induction (50% vs 43%; 66% vs 88%; respectively) and a superior TRM in induction (33% vs 22%; 67% vs 56%; respectively) compared to the others T-ALL but without significant differences. Pediatric population ETP-ALL have a higher relapse rate (100% vs 42%; p=0.245) and an inferior OS and EFS at 3 years (0% vs 53% and 0% vs 54% with p<0.001, respectively). Summary/Conclusion: Our study highlighted the challenges of diagnosis and prognostic of ETP-ALL. In fact, Auer rods like inclusions in the mature neutrophils found in blood smears, extremely rare in ETP-ALL, can turn the diagnosis towards AML. FCI with a large panel is essential to rule out a possibility of underlying mixed phenotype acute leukemia or ALL. ETP-ALL appear to have an obvious prognostic impact in our study in pediatric population (OS and EFS) as reported in the literature. Therefore, a larger study should be conducted to better understand the prognosis of this disease and plan the treatment. Keywords: Chemotherapy, T cell acute lymphoblastic leukemia, Flow cytometry